1. Field of the Invention
The present invention relates generally to the fields of neurobiology and neurodegenerative diseases. More particularly, it concerns the development of screening methods to detect and identify candidate molecules that confer neuroprotective effects following toxin-induced neuronal damage. The invention describes in vivo screening protocols using a recombinant C. elegans that expresses a detectable marker in sub-groups of neurons, such as, dopaminergic neurons.
2. Description of Related Art
Neurodegenerative diseases, strokes and neuronal injuries caused by trauma are typically characterized by neuronal cell death of groups of neurons. Among these neurological disorders, neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, etc., afflict a large percentage of the population. For example, Alzheimer's disease alone afflicts about 4 million people in the United States, primarily the elderly, and is characterized by progressive memory loss, disorientation, depression and eventual loss of other body functions. Amyotrophic lateral sclerosis afflicts about 30,000 Americans, typically begins after age 40 and results in progressive weakness and paralysis. Huntington's Disease afflicts an estimated 25,000 patients in the United States, usually begins between the ages of 30 and 50 and includes violent, involuntary movements. Parkinson's Disease (PD) affects over 1 million people in the United States, and also usually begins on or after age 50. PD is another progressive disorder of the central nervous system and is characterized by a decrease in spontaneous movements, gait difficulty, postural instability, rigidity and tremor due to the degeneration of dopaminergic neurons.
In spite of great effort, little is known about the molecular basis of these disorders. Although the use of vertebrate and tissue culture systems continue to provide valuable insight into the pathology of the neurodegeneration, the molecular determinants involved in the etiology of these diseases remain elusive. As a result, there is an acute deficiency of effective therapeutic agents to treat these neurodegenerative disorders.
Although several drugs currently are being used for treatment of these diseases, none of these drugs offer complete cure or reversal of these disorders. In fact, most drugs only temporarily relieve some of the symptoms associated with the disease and do not prevent further degeneration of neurons. Hence, these disorders have been termed as progressive neurological disorders. Thus, the main goal of researchers in this field is to identify agents that will provide preventive as well as therapeutic relief for such diseases. At present, there is no effective high-throughput method to identify molecules with neuroprotective abilities in vivo.